TWI672486B - Cartridge and analyzer for fluid analysis - Google Patents

Abstract

This disclosure describes a liquid box and a method of operation. The liquid box body includes a substrate having a plurality of contact pads designed to be electrically coupled to an analyzer, a semiconductor wafer having a sensor array, and a reference electrode. The liquid box body includes a first liquid channel, the first liquid channel has an inlet and is coupled to a second liquid channel, and the second liquid channel is aligned so that the sensor array and the reference electrode are placed on the first Two liquid channels. A first plug is placed at the first entrance. The first plug comprises a flexible material configured to be pierced by a capillary but not to allow liquid to leak through the first plug.

Description

Case and analyzer for analyzing liquid

The embodiment of the invention relates to a box body and an analyzer for analyzing liquid.

Biosensors are devices used to sense and detect biomolecules and operate on the basis of electronic, electrochemical, optical, and mechanical detection principles. Biosensors including transistors are sensors that sense the electrical properties of charge, photons, and the mechanical properties of biological entities or biomolecules. Detection can be performed by detecting biological entities or biomolecules themselves or through interactions and reactions between designated reactants and biological entities / biomolecules. Such biosensors can be manufactured using semiconductor programs, can quickly convert electrical signals, and can be easily applied to integrated circuits (ICs) and MEMS. The interaction of the biological sample itself with the biosensor can be a challenge. Generally, a liquid containing a biological sample is pipetted directly above the sensing portion of the biosensor. This method results in most of the liquid samples being unused and manual loading of each sensing area is time consuming.

According to an embodiment of the present invention, a liquid box body includes a substrate including a plurality of contact pads configured to be electrically coupled with an analyzer, a semiconductor wafer having a sensor array. And a reference electrode; a first liquid channel having a first inlet and coupled to a second liquid channel, the second liquid channel is aligned such that the sensor array and the reference electrode are placed on the second A liquid inlet; a sample inlet for placing a sample in one of the first liquid channel or the second liquid channel; and a first plug that is placed at the first inlet and includes a A flexible material configured to be pierced by a capillary but not to allow liquid to leak through the first plug. According to another embodiment of the present invention, a liquid box body includes: a first liquid channel having a first inlet and coupled to a second liquid channel, the second liquid channel is aligned so that a sensor array And a reference electrode is placed in the second liquid channel; a sample inlet is used to place a sample in a path of the first liquid channel or the second liquid channel; and a first plug is placed At the first inlet and includes a flexible material configured to be pierced by a capillary but not to allow liquid to leak through the first plug, wherein the capillary is coupled to an analyzer, and wherein when the liquid is made The capillary penetrates the first plug when the box body is in contact with the analyzer entity. According to yet another embodiment of the present invention, an analyzer configured to couple with a liquid cartridge includes: a syringe configured such that when the liquid cartridge is physically coupled to the analyzer a needle Aligned with one of the corresponding input ports of the liquid box; an actuator configured to control the operation of the syringe; a sensing module configured to send and receive liquid from the liquid via a plurality of conductive pads A signal of the box body, when the liquid box body is physically coupled to the analyzer, the plurality of conductive pads contact the corresponding plurality of conductive pads on the liquid box body; and a processor, which is electrically coupled to the sensing module And configured to determine a concentration level of a given analyte from a sample in a liquid cartridge based on a signal received from the liquid cartridge.

The following disclosure provides many different embodiments or examples that provide different components for implementing the provided subject matter. Specific examples of components and configurations are described below to simplify this disclosure. Of course, these are merely examples and are not intended to be limiting. For example, in the following description, a first component formed over a second component may include an embodiment in which the first component and the second component are formed in direct contact, and may also include an embodiment in which additional components may be formed and / or An embodiment in which it is placed between the first member and the second member so that the first member and the second member cannot be in direct contact. In addition, the present disclosure may repeat element symbols and / or letters in various examples. This repetition does not in itself indicate a relationship between the various embodiments and / or configurations discussed. Further, for convenience of explanation, spatially relative terms (such as "below", "below", "lower", "above", "upper" and the like) may be used herein to describe an element or The relationship of a component to another element (s) or component is as illustrated in the figures. These spatial relative terms are intended to encompass different orientations of the device in use or operation in addition to the orientations illustrated in the figures. The device may be otherwise oriented (eg, rotated 90 degrees or at other orientations) and the spatially relative narratives used herein may equally be interpreted accordingly. Terminology Unless defined otherwise, all technical and scientific terms used herein have the same meaning as commonly understood by one of ordinary skill in the art to which this disclosure belongs. Although any methods and materials similar or equivalent to those described herein can be used in the practice or testing of the embodiments in accordance with the present disclosure, the methods, devices, and materials are now described. For the purpose of clarifying and disclosing the materials and methods reported in the publications used in connection with this disclosure, all patents and publications mentioned herein are incorporated herein by reference. The acronym "FET" as used herein refers to a field effect transistor. A very common type of FET is called a metal oxide semiconductor field effect transistor (MOSFET). Historically, MOSFETs have been planar structures constructed in and on a planar surface such as a substrate of a semiconductor wafer. But recent advances in semiconductor manufacturing have produced three-dimensional fin-based MOSFET structures. The term "bioFET" refers to a FET comprising a layer of an immobilized capture reagent that acts as a surface receptor to detect the presence of a target analyte of biological origin. According to an embodiment, a bio-FET system has a semiconductor-effect field-effect sensor. One advantage of bioFETs is the desire for label-free operation. In particular, bioFETs make it possible to avoid expensive and time-consuming labeling operations, such as labeling an analyte with, for example, a fluorescent or radioactive probe. A particular type of bioFET described in this article is a dual-gate backside sensing bioFET. Analytes for detection by a bioFET will typically be of biological origin, such as (without limitation) proteins, carbohydrates, lipids, tissue fragments, or portions thereof. However, in a more general sense, a bio-FET system can also detect any chemical compound as part of a broader FET sensor (referred to as a chemical FET in this technology) or contains components such as protons or metal ions Any other element of the ion (referred to in the art as an ISFET). This disclosure is intended to apply to all types of FET-based sensors ("FET sensors"). One particular type of FET sensor in this article is a dual-gate backside sensing FET sensor ("DG BSS FET sensor"). "S / D" refers to the source / drain junction of two of the four terminals forming a FET. The expression "high k" refers to a high dielectric constant. In the field of semiconductor device structure and manufacturing procedures, high k refers to a dielectric constant that is greater than the dielectric constant of SiO ₂ (ie, greater than 3.9). The term "analysis" generally refers to a procedure or step involving physical, chemical, biochemical, or biological analysis, which includes, but is not limited to, characterization, testing, measurement, optimization, separation, synthesis, addition, filtration, dissolution or mixing . The term `` assay '' generally refers to a procedure or step involving the analysis of a chemical or a target analyte and includes but is not limited to cell-based assays, biochemical assays, high-throughput assays and screening, diagnostic assays, pH determination, Nucleic acid hybridization assays, polymerase activity assays, nucleic acid and protein sequencing, immunoassays (e.g., antibody-antigen binding assays, ELISA and iqPCR), bisulfite methylation to detect methylation patterns of genes Assays, protein assays, protein binding assays (e.g., protein-protein, protein-nucleic acid, and protein-ligand binding assays), enzyme assays, coupling enzyme assays, kinetic measurements (e.g., protein folding kinetics and enzyme reaction kinetics ), Enzyme inhibitor and activator screening, chemiluminescence and electroluminescence assays, fluorescence assays, fluorescence polarization and anisotropy assays, absorbance and colorimetric assays (e.g. Bradford assay, Lowry (Lowry test, Hartree-Lowry test, Biuret test, and BCA test), chemical tests (e.g., for detecting environmental pollutants and pollution, nanometers Particles or polymers) and drug discovery tests. The devices, systems, and methods described herein can use or employ one or more of these assays for use with any of the designs described by FET sensors. The term "fluid biopsy" generally refers to a biopsy sample obtained from a subject's body fluid compared to a subject's tissue sample. The ability to perform an assay using a single fluid sample is often more desirable than using a tissue sample. Low-invasive methods using a single-fluid sample have a wide range of benefits in terms of patient welfare, the ability to monitor longitudinal disease, and the ability to obtain expression profiles even when tissue cell lines are not easily accessible (e.g., in the prostate). meaning. Assays for detecting target analytes in fluid biopsy samples include, but are not limited to, those described above. As a non-limiting example, a fluid biopsy sample can be subjected to a circulating tumor cell (CTC) assay. For example, a capture reagent (e.g., an antibody) immobilized on a FET sensor can be used to detect a target analyte (e.g., a tumor cell marker) in a fluid biopsy sample using a CTC assay ). CTCs are cells that have spread from a tumor into a blood vessel and, for example, circulate in the bloodstream. In general, CTC is present in the circulation at extremely low concentrations. To characterize CTCs, CTCs are enriched from the patient's blood or plasma by various techniques known in the art. CTCs can be stained for specific markers using methods known in the art, including, but not limited to, cytometry-based (eg, flow cytometry) methods and IHC-based methods. For the devices, systems, and methods described herein, a capture reagent can be used to capture or detect CTCs or nucleic acids, proteins, or other cell surroundings from CTCs can be targeted for binding to or by a capture reagent. Detected target analyte. When detecting a target analyte on or from a CTC, for example, the addition of one of the target analytes expressing or containing CTC can help identify a subject as having the potential to be associated with a particular treatment (e.g., it is associated with a The target analyte is associated) to respond to one of the cancers or to allow, for example, optimization of a treatment regimen with an antibody to the target analyte. CTC measurement and quantification can provide information on, for example, tumor stage, response to treatment, disease progression, or a combination thereof. Information obtained from detecting target analytes on CTCs can be used, for example, as a prognostic, predictive, or medicinal biomarker. In addition, the CTC assay on a fluid biopsy sample can be used alone or in combination with additional tumor marker analysis on a solid biopsy sample. The term "identification" generally refers to a process for determining the identity of a target analyte based on a combination of the target analyte and a capture reagent (whose identity is known). The term "measurement" generally refers to a procedure for determining the amount, quantity, quality, or nature of a target analyte based on a combination of the target analyte and a capture reagent. The term "quantification" generally refers to a procedure for determining the quantity or concentration of a target analyte based on a combination of the target analyte and a capture reagent. The term "detection" generally refers to a procedure for determining the presence or absence of a target analyte based on a combination of the target analyte and a capture reagent. Detection includes, but is not limited to, identification, measurement, and quantification. The term "chemical" refers to a substance, compound, mixture, solution, emulsion, dispersion, molecule, ion, dimer, macromolecule such as a polymer or protein, biomolecule, precipitate, crystal, chemical moiety Or groups, particles, nano particles, reagents, reaction products, solvents or liquids, any of which can exist in a solid, fluid or gas state and are usually the subject of analysis. The term "reaction" refers to a physical, chemical, biochemical, or biotransformation that involves at least one chemical and generally involves (in the case of chemical, biochemical, and biotransformation) such as Break or formation of one or more of van der Waals, hydrogen or ionic bonds. The term encompasses typical chemical reactions such as synthetic reactions, neutralization reactions, decomposition reactions, displacement reactions, redox reactions, precipitation, crystallization, combustion reactions, and polymerization reactions, as well as covalent and non-covalent binding, phase changes, color changes, Phase formation, crystallization, dissolution, light emission, change in light absorption or emission properties, temperature change or heat absorption or emission, change in configuration, and folding or unfolding of a giant molecule such as a protein. As used herein, a "capture reagent" is a molecule or compound capable of binding a target analyte or target reagent that can be directly or indirectly attached to a substantially solid material. The capture reagent may be a chemical, and in particular, for the presence of a naturally occurring target analyte (eg, an antibody, polypeptide, DNA, RNA, cell, virus, etc.) or for which a target analyte may be prepared. Either substance and the capture reagent can bind to one or more target analytes in an assay. As used herein, a "target analyte" is a substance that will be detected in a test sample using this disclosure. The target analyte can be a compound, and specifically any one for which the presence of a naturally occurring capture reagent (eg, an antibody, polypeptide, DNA, RNA, cell, virus, etc.) or for which a capture reagent can be prepared Substance, and the target analyte can be bound to one or more capture reagents in an assay. A "target analyte" also includes any antigenic substance, antibody, and combination thereof. The target analyte can include one of a protein, a peptide, an amino acid, a carbohydrate, a hormone, a steroid, a vitamin, one that is performed for therapeutic purposes, and one that is performed for illegal purposes. A drug, a bacterium, a virus, or a metabolite or antibody of any of the above. A "test sample" as used herein means a composition, solution, substance, gas, or fluid containing a target analyte that will be detected and characterized using this disclosure. The test sample may contain components other than the target analyte, may have the physical properties of a fluid or a gas, and may be of any size or volume, including, for example, a moving fluid or gas stream. The test sample may contain any substance other than the target analyte as long as the other substances do not interfere with the binding of the target analyte with the capture reagent or the specific binding of the first binding member to the second binding member. Examples of test samples include, but are not limited to, naturally occurring and non-naturally occurring samples or combinations thereof. Naturally generated test samples can be synthetic or synthetic. Naturally generated test samples contain body fluid or bodily fluid isolated from or on the subject's body, including but not limited to blood, plasma, serum, urine, saliva or sputum, spinal fluid, cerebral spinal Fluid, pleural fluid, nipple aspirate, lymph fluid, respiratory fluid, intestinal and genitourinary fluids, tears, saliva, breast milk, fluids from the lymphatic system, semen, cerebrospinal fluid, fluids in organ systems, ascites, tumor sacs Fluid, amniotic fluid, and combinations thereof, and environmental samples such as groundwater or wastewater, soil extracts, air and pesticide residues, or food-related samples. The detected substance may include, for example, nucleic acids (including DNA and RNA), hormones, different pathogens (including a biological agent that causes a disease or illness in their host, such as a virus (for example, H7N9 or HIV), a protozoa (For example, malaria caused by Plasmodium) or a bacterium (for example, E. coli or Mycobacterium tuberculosis), proteins, antibodies, various drugs or treatments or other chemical or biological substances, including hydrogen or other ionic, non-ionic molecules Or compounds, polysaccharides, small chemical compounds such as members of chemical combinatorial libraries, and the like. The detected or determined parameters may include, but are not limited to, for example, pH changes, lactose changes, changed concentrations, particles per unit time (where a liquid flows over the device for a period of time to detect particles, such as sparse Particles) and other parameters. As used herein, the term "immobilization" when used in connection with, for example, a capture reagent includes substantially attaching a capture reagent at a molecular level to a surface. For example, a capture reagent can be immobilized to a surface of a substrate material using adsorption techniques that include non-covalent interactions (e.g., electrostatic forces, dehydration of Van der Waals and hydrophobic interfaces) and their functional groups. Clusters or linkers facilitate covalent binding techniques that attach capture reagents to a surface. Immobilizing a capture reagent to a surface of a substrate material may be based on the properties of the substrate surface, the medium that carries the capture reagent, and the properties of the capture reagent. In some cases, a substrate surface may be modified first to allow functional groups to bind to the surface. The functional groups may then be bound to a biomolecule or a biological or chemical substance to immobilize the functional groups thereon. The term "nucleic acid" generally refers to a collection of nucleotides linked to each other via a phosphodiester bond and refers to a naturally occurring nucleic acid linked to a naturally occurring nucleotide that exists in nature, such as including adenine, guanine, DNA of deoxynucleotides linked to any of cytosine and thymine and / or RNA including ribonucleotides linked to any of adenine, guanine, cytosine and uracil. In addition, non-naturally occurring nucleotides and non-naturally occurring nucleic acids are within the scope of the nucleic acids disclosed herein. Examples include peptide nucleic acids (PNA), peptide nucleic acids (PHONA) with phosphate groups, bridged nucleic acids / locked nucleic acids (BNA / LNA), and morpholinyl nucleic acids. Further examples include chemically modified nucleic acids and nucleic acid analogs, such as methylphosphonate DNA / RNA, phosphorothioate DNA / RNA, phosphoramidate DNA / RNA, and 2'-0-methyl DNA / RNA. Nucleic acids include those nucleic acids that can be modified. For example, a phosphate group, a sugar and / or a base in a nucleic acid may be labeled as necessary. Any substance used in nucleic acid labeling known in the art can be used for labeling. Examples include, but are not limited to, radioisotopes (e.g., 32P, 3H, and 14C), DIG, biotin, fluorescent dyes (e.g., FITC, Texas, cy3, cy5, cy7, FAM, HEX, VIC, JOE, Rox, TET , Bodipy493, NBD and TAMRA) and luminescent substances (eg, acridinium esters). As used herein, an adaptation system refers to an oligonucleotide or peptide molecule that binds to a specific target molecule. The concept of using single-stranded nucleic acids (aptamers) as affinity molecules for protein binding was first revealed in 1990 (Ellington and Szostak 1990, 1992; Tuerk and Gold 1990), and was based on the existence of a goal The ability to fold short sequences into unique three-dimensional structures that bind to targets with high affinity and specificity. Eugene W. M Ng et al., In 2006, disclosed an oligonucleotide ligand that the adaptation system was selected for high affinity binding to molecular targets. The term "antibody" as used herein refers to a polypeptide of the immunoglobulin family capable of non-covalently, reversibly and in a specific manner binding a corresponding antigen. For example, a naturally occurring IgG antibody system includes a tetramer of at least two heavy (H) chains and two light (L) chains interconnected by disulfide bonds. Each heavy chain includes a heavy chain variable region (abbreviated herein as VH) and a heavy chain constant region. The heavy chain constant region includes three domains: CH1, CH2, and CH3. Each light chain includes a light chain variable region (abbreviated herein as VL) and a light chain constant region. The light chain constant region includes a domain CL. The VH and VL regions can be further subdivided into hypervariable regions (referred to as complementarity determining regions (CDR)) and more conservative regions (referred to as framework regions (FR)), which are interspersed. Each VH and VL is composed of three CDRs and four FRs, which are arranged in the following order from the amine terminal to the carboxy terminal: FR1, CDR1, FR2, CDR2, FR3, CDR3, and FR4. These three CDRs constitute approximately 15% to 20% of the variable domain. The variable regions of the heavy and light chains contain a binding domain that interacts with an antigen. The constant region of an antibody can mediate the binding of immunoglobulins to host tissues or factors (including various cells of the immune system (eg, effector cells) and the first component (C1q) of the classical complement system). (Kuby Immunology, Fourth Edition, Chapter 4, WH Freeman & Co., New York, 2000). The term "antibody" includes, but is not limited to, monoclonal antibodies, human antibodies, humanized antibodies, chimeric antibodies, and anti-Id antibodies (eg, anti-genetic antibodies including the antibodies disclosed herein). The antibodies can be of any isotype / class (e.g., IgG, IgE, IgM, IgD, IgA, and IgY) or subclasses (e.g., IgG1, IgG2, IgG3, IgG4, IgA1, and IgA2). The term "polymer" means any substance or compound consisting of two or more building blocks ("monomer units") that are repeatedly linked to each other. For example, a "dimer" is a compound in which two building elements have been joined together. The polymer includes both a condensation polymer and an addition polymer. Typical examples of the condensation polymer include polyamide, polyester, protein, wool, silk, polyurethane, cellulose, and polysiloxane. Examples of addition polymers are polyethylene, polyisobutylene, polyacrylonitrile, poly (vinyl chloride), and polystyrene. Other examples include polymers having enhanced electrical or optical properties (e.g., a non-linear optical property), such as conductive or photorefractive polymers. The polymer includes both linear polymers and branched polymers. Overview of the Biosensor Cassette FIG. 1 illustrates an overview of one of the various components integrated together to form an exemplary biosensor cassette 102. The biosensor cartridge 102 may include a plurality of liquid channels configured to control the flow of liquid both toward and away from a sensing location in which the presence of a target analyte can be detected. In this illustrative embodiment, the biosensor box 102 includes an array of FET sensors 104. The FET sensor 104 constitutes a sensor component of the biosensor box 102. The FET sensors 104 may be configured as an array and individually addressed to detect bonding events at the surface of the FET sensor sensing layer. In one embodiment, the FET sensor 104 includes a dual-gate backside FET sensor. In alternative embodiments, other types of FET-based sensors may be used. The biosensor box 102 includes a biological interface 106. The biological interface 106 can be coupled to the double-gate backside sensing FET sensor 104 to promote a binding reaction at the surface of the double-gate backside sensing FET sensor 104, and then the binding reaction can be detected. Various types of biomolecules can form part of the biological interface 106, such as DNA or RNA aptamers and antibodies (to name a few). Further details on the biological interface and its associated chemistry and biomechanics are discussed in detail in this article. The biosensor box 102 includes various levels of chip packages 108 to integrate a dual-gate backside sensing FET sensor chip into a liquid environment. The biosensor cartridge 102 also includes a liquid component 110 with a microfluidic channel to manage the delivery of fluid to the FET sensor 104. The liquid assembly 110 also incorporates a liquid inlet for interfacing with liquid delivered from the outside of the biosensor cartridge 102. The integration of various components in the biosensor box 102 results in a compact and portable platform that can be used in one of many various biosensor applications. Using FET sensors with integrated liquid components produces accurate results when using low sample volumes. In addition, the biosensor cartridge 102 can be configured to operate in a fully automatic manner by an analyzer, and then disposed of after use. The description herein is divided into four main sections to further elaborate the components of the biosensor cartridge 102. The first section will explain the configuration and fabrication of the dual-gate backside bioFET sensor 104. The second chapter will explain the packaging procedure. The third section will explain the liquid assembly 110, and further explain the interaction between the biosensor box 102 and an analyzer. The last chapter will provide details on the biology and various biosensing applications using the dual-gate backside FET sensor 104. Double-Gate Backside FET Sensor The double-gate backside FET sensor uses semiconductor manufacturing technology and biological capture reagents to form a sensitive and easy-to-align sensor. Although a conventional MOSFET has a single gate electrode connected to one of a single electrical node, a dual-gate backside sensing FET sensor has two gate electrodes, each of the two gate electrodes being connected to a Different electrical nodes. A first gate electrode of one of the two gate electrodes is referred to herein as a front-side gate and a second gate electrode of the two gate electrodes is referred to herein as a back-side gate. Both the front gate and the back gate are configured so that each gate can be electrically charged and / or discharged during operation and therefore each gate affects the source of the dual gate backside sensing FET sensor The electric field between the pole / drain terminals. The front-side gate is conductive, separated from a channel region by a front-side gate dielectric, and configured to be charged and discharged by a circuit coupled by the front-side gate. The back gate is usually separated from the channel region by a back gate dielectric and includes a bio-functionalized sensing layer placed on the back gate dielectric. The amount of charge on the back gate is a function of whether a biometric response has occurred. In a typical operation of a dual-gate backside sensing FET sensor, the front-side gate is charged to a voltage within a predetermined voltage range. This voltage on the front gate determines the corresponding conductivity of one of the channel regions of the FET sensor. A relatively small change in one of the charges on the backside gate changes the conductivity of the channel region. This change in conductivity is indicative of a biometric response. One advantage of FET sensors is the desire for tag-free operation. In particular, FET sensors make it possible to avoid expensive and time-consuming labeling operations, such as labeling an analyte with, for example, a fluorescent or radioactive probe. Referring to FIG. 2, an exemplary dual-gate backside sensing FET sensor 200 is illustrated. The dual-gate backside sensing FET sensor 200 includes a gate 202 that is formed above the substrate 214 and is separated from the substrate 214 by an intervening dielectric 215 placed on the substrate 214. The substrate 214 further includes a source region 204, a drain region 206, and a channel region 208 between the source region 204 and the drain region 206. In one embodiment, the substrate 214 has a thickness between about 100 nm and about 130 nm. Gate 202, source region 204, drain region 206, and channel region 208 may be formed using a suitable CMOS process technology. The gate 202, the source region 204, the drain region 206, and the channel region 208 form a FET. An isolation layer 210 is placed on the substrate 214 on the side opposite to the gate electrode 202. In one embodiment, the isolation layer 210 has a thickness of about 1 μm. In the present disclosure, the side of the substrate 214 on which the gate electrode 202 is placed is referred to as the “front side” of the substrate 214. Similarly, the side of the substrate 214 on which the isolation layer 210 is placed is referred to as the "back side". An opening 212 is provided in the isolation layer 210. The opening 212 may be substantially aligned with the gate electrode 202. In other embodiments, the opening 212 is larger than the gate 202 and may extend over a plurality of double-gate backside sensing FET sensors. An interface layer (not shown) may be placed in the opening 212 on the surface of the channel region 208. The interface layer is operable to provide an interface for locating and immobilizing one or more receptors for detecting a biological molecule or biological entity. Further details on the interface layer are provided in this article. The dual gate backside sensing FET sensor 200 includes a drain region 206 (Vd 216), a source region 204 (Vs 218), a gate structure 202 (front gate 220), and / or an active region 208 (e.g., , The electrical contacts of the back gate 222). It should be noted that the back gate 222 does not need to physically contact the substrate 214 or any interface layer above the substrate 214. Therefore, although a conventional FET uses a gate contact to control the conductivity of a semiconductor (for example, a channel) between a source and a drain, the dual-gate backside sensing FET sensor 200 allows formation in a FET device The receptor on the opposite side controls the conductivity, while the gate structure 202 provides another gate to control the conductivity. Therefore, the dual-gate backside sensing FET sensor 200 can be used to detect one or more specific biomolecules or biological entities in and / or around the opening 212, as described in more detail using various examples herein Exposition. Dual-gate backside sensing FET sensor 200 can be connected to additional passive components such as resistors, capacitors, inductors and / or fuses; and other active components including P-channel field effect transistors (PFETs), N Channel field effect transistor (NFET), metal oxide semiconductor field effect transistor (MOSFET), high voltage transistor and / or high frequency transistor; other suitable components; and / or combinations thereof. It should be further understood that additional components may be added to the dual-gate backside sensing FET sensor 200, and additional embodiments for the dual-gate backside sensing FET sensor 200 may replace or delete the components described Some of the building blocks. Further details regarding an example fabrication process for the dual-gate backside sensing FET sensor 200 may exist in co-owned US Patent Application No. 2013/0200438 and US Patent Application No. 2014/0252421. Referring to FIG. 3, a schematic diagram of an exemplary addressable array 300 of a FET sensor 304 connected to a bit line 306 and a word line 308 is illustrated. It should be noted that the terms bit line and word line are used herein to indicate similarities to the array structure in a memory device, however, it does not imply that a memory device or a storage array must be included in the array. Addressable array 300 may have similarities to arrays used in other semiconductor devices, such as dynamic random access memory (DRAM) arrays. For example, the dual-gate backside sensing FET sensor 200 described above with reference to FIG. 2 may be formed in a position where a capacitor will exist in a DRAM array. The diagram 300 is merely exemplary and it will be recognized that other configurations are possible. The FET sensors 304 may each be substantially similar to the double-gate backside sensing FET sensor 200. The FET 302 is configured to provide a connection between one of the drain terminals of the FET sensor 304 and the bit line 306. In this manner, the FET 302 is similar to an access transistor in a DRAM array. In this exemplary embodiment, the FET sensor 304 is a dual-gate backside sensing FET sensor and includes a dielectric layer overlying an FET active area (placed at a reaction site). A sensing gate provided by an acceptor material on the electrical layer, and a control gate provided by a gate electrode (e.g., polycrystalline silicon) placed on a dielectric layer overlying the active area of the FET pole. Schematic diagram 300 shows an array formation that can be advantageous in detecting small signal changes provided by the smallest biomolecule or biological entity introduced into the FET sensor 304. The use of an arrangement of bit lines 306 and word lines 308 allows a reduction in the number of input / output pads. The amplifier can be used to enhance the signal strength to improve the detection capability of the device with the circuit configuration of the schematic diagram 300. In one embodiment, when the specific word line 308 and bit line 306 are verified, the corresponding access transistor 302 is turned on (for example, like a switch). When the gate of the associated FET sensor 304 (e.g., such as the back gate 222 of the dual-gate backside sensing FET sensor 200) has its charge affected by the presence of biomolecules, the FET sensor 304 will The electrons are transferred and cause field effect charging of the device, thus modulating the current (eg, I _ds ). Changes in current (eg, I _ds ) or threshold voltage (V _t ) can be used to indicate the detection of related biomolecules or biological entities. Therefore, a device with a schematic diagram 300 can achieve a biosensor application, including an application with differential sensing for enhanced sensitivity. Referring to FIG. 4, an exemplary layout 400 is presented. The exemplary layout 400 includes an access transistor 302 and an FET sensor 304 configured as an array 401 of individually addressable pixels 402. The array 401 may include any number of pixels 402. For example, the array 401 may include 128 × 128 pixels. Other configurations may include 256 × 256 pixels or non-square arrays, such as 128 × 256 pixels. Each pixel 402 includes an access transistor 302 and a dual-gate backside sensing FET sensor 304 along with other components that may include one or more heaters 408 and a temperature sensor 410. In this example, the access transistor 302 is an n-channel FET. An n-channel FET 412 can also act as an access transistor for the temperature sensor 410. In the illustrative example, the gates of FETs 302 and 412 are commonly coupled, although this is not required. Each pixel 402 (and its associated components) may be individually addressed using a row decoder 406 and a column decoder 404. In one example, each pixel 402 has a size of about 10 microns by about 10 microns. In another example, each pixel 402 has a size of about 5 microns by about 5 microns, or a size of about 2 microns by about 2 microns. The row decoder 406 and the column decoder 404 can be used to determine the on / off states of the n-channel FETs 302 and 412. Turning on the n-channel FET 302 provides a current to an S / D region of the double-gate backside sensing FET sensor 304. When these devices are turned on, a current I _ds flows through the FET sensor 304 and can be measured. The heater 408 may be used to locally increase a temperature around a double-gate backside sensing FET sensor 304. The heater 408 may be constructed using any known technique, such as forming a metal model with one of the high currents traveling through it. The heater 408 may also be a thermoelectric heater / cooler, such as the same Peltier device. The heater 408 may be used during specific biological tests to denature DNA or RNA or to provide a more ideal binding environment for specific biological molecules. The temperature sensor 410 can be used to measure a local temperature around the dual-gate backside sensing FET sensor 304. In one embodiment, a control loop may be formed to control the temperature using the heater 408 and the feedback received from the temperature sensor 410. In another embodiment, the heater 408 may be a thermoelectric heater / cooler that allows local active cooling of components within the pixel 402. Referring to FIG. 5, a cross-section of an exemplary dual-gate backside sensing FET sensor 500 is provided. The dual-gate backside sensing FET sensor 500 is an implementation of the dual-gate backside sensing FET sensor 200, so the components from FIG. 2 previously labeled with the component symbols from FIG. 2 are labeled and The description of these components is not repeated here. The dual-gate backside sensing FET sensor 500 includes a gate 202, a source region 204, a drain region 206, and a channel region 208. The source region 204 and the drain region 206 are formed in the substrate 214. The gate 202, the source region 204, the drain region 206, and the channel region 208 form a FET. It should be noted that the various components of FIG. 5 are not intended to be drawn to scale and are enlarged for visual convenience, as those skilled in the relevant art will understand. In an exemplary embodiment, the dual-gate backside sensing FET sensor 500 is coupled to various layers of the metal interconnect 502 that are electrically connected to various doped regions and other devices formed within the substrate 214. The metal interconnect 502 can be manufactured using manufacturing procedures well known to those skilled in the relevant art. The dual-gate backside FET sensor 500 may include a body region 504 separate from the source region 204 and the drain region 206. The body region 504 can be used to bias the carrier concentration in the active region 208 between the source region 204 and the drain region 206. As such, a negative voltage bias can be applied to the body region 504 to improve the sensitivity of the dual-gate backside FET sensor 500. In one embodiment, the body region 504 is electrically connected to the source region 204. In another embodiment, the body region 504 is electrically grounded. The dual-gate backside FET sensor 500 may be coupled to an additional circuit 506 fabricated in the substrate 214. The circuit 506 may include any number of MOSFET devices, resistors, capacitors, or inductors to form circuits to assist the operation of the dual-gate backside sensing FET sensor 500. For example, the row decoder 406 and the column decoder 404 may be formed in the circuit 506. The circuit 506 may include any amplifier, analog / digital converter (ADC), digital / analog converter (DAC), voltage generator, logic circuit, and DRAM memory (to name a few). All or some of the components of the additional circuit 506 may be integrated in the same substrate 214 as the dual-gate backside FET sensor 500. It should be understood that many FET sensors (each substantially similar to the dual-gate backside FET sensor 500) may be integrated on the substrate 214 and coupled to the additional circuit 506. In another example, all or some of the components of the additional circuit 506 are provided on another semiconductor substrate separate from the substrate 214. In yet another example, certain components of the additional circuit 506 are integrated in the same substrate 214 as the dual-gate backside FET sensor 500, and some components of the additional circuit 506 are provided on another semiconductor separate from the substrate 214 On the substrate. Still referring to the illustrative example of FIG. 5, the dual-gate backside sensing FET sensor 500 includes an interface layer 508 deposited over the isolation layer 210 and in an opening above the channel region 208. In one embodiment, the interface layer 508 has a thickness between about 20 Å and about 40 Å. The interface layer 508 may be a high-K dielectric material, such as hafnium silicate, hafnium oxide, zirconia, alumina, tantalum pentoxide, hafnium dioxide-alumina (HfO ₂ -Al ₂ O ₃ ) alloy or any of them combination. The interface layer 508 may serve as a support for attaching a capture reagent, as will be discussed in more detail later in the section for biosensing. An example operation of a dual-gate backside FET sensor 500 serving as a pH sensor will now be described. In short, a liquid gate 510 is used to provide an electrical contact to the "second gate" of the dual-gate backside sensing FET sensor. A solution 512 having a given pH is provided above the reaction site of the dual-gate backside sensing FET sensor 500, and the liquid gate 510 is placed in the solution 512. The pH of a solution is generally related to the concentration of hydrogen ions [H ⁺ ] in the solution. The accumulation of ions near the surface of the interface layer 508 above the channel region 208 will affect the formation of the inversion layer in the channel region 208 that forms a conductive path between the source region 204 and the drain region 206. This can be measured by a change in the conductivity of the FET sensor. In one embodiment, the liquid gate 510 acts as a gate for the transistor and the gate 202 remains floating during sensing. In another embodiment, the liquid gate 510 is used as the gate of the transistor and the gate 202 is biased at a given potential during sensing. For example, the gate 202 may be biased at a potential between -2V and 2V depending on the application, while the liquid gate 510 is flicked between a voltage range. In another embodiment, the liquid gate 510 is biased (or grounded) at a given potential and the gate 202 is used as the gate of the transistor during sensing (for example, its voltage is flicked across a range of potentials) . The liquid gate 510 may be formed of platinum or may be formed of any other material commonly used for reference electrodes in electrochemical analysis. The most common reference electrode is an Ag / AgCl electrode with a stable potential value of about 0.230 V. FIG. 6A shows that ions in the solution are bound to one surface of the interface layer 508. One of the interface layer 508 topmost atomic layers were depicted as various suspension [O ^-], [OH] and [OH ₂ ^+] key. Because ions accumulate on the surface, the total surface charge affects the threshold voltage of the transistor. As used herein, the threshold voltage is the minimum required between the gate and source of the FET sensor required to form a minority carrier conduction path between the source and the drain of the FET sensor. Potential. The total charge is also directly related to the pH of the solution, because a higher accumulation of a positive charge indicates a lower pH and a higher accumulation of a negative charge indicates a higher pH. FIG. 6B illustrates changes in threshold voltage due to different pH values in an n-channel FET sensor. As can be seen in the figure, a 59 mV increase in one of the threshold voltages roughly indicates an increase in one of the pHs of the solution. In other words, a pH change produces a total surface charge equivalent to 59 mV when measured as the voltage required to turn on the transistor. Wafer Package Referring to FIG. 7, an exemplary plan view of a semiconductor wafer 702 is shown. The chip 702 includes a sensor array 704, an optional reference electrode 706, an analog circuit 708, and an I / O pad 716. The chip 702 may be silicon, gallium arsenide, or indium phosphide (to name a few). The wafer 702 may have a size of about 3 mm by about 2.5 mm. The sensor array 704 represents an array of dual-gate backside sensing FET sensors such as those illustrated above in FIGS. 2 and 5. The array may be configured as a column-row matrix of pixels as illustrated, for example, in FIG. 4. Various FET sensors in the sensor array 704 can be functionalized with the same or different capture reagents to perform biosensing of various analytes. The reference electrode 706 may be patterned on the same wafer 702 including the sensor array 704. The reference electrode 706 can be substantially aligned with the sensor array 704 along an X or Y direction, so that a liquid channel can be placed over both the sensor array 704 and the reference electrode 706. In another embodiment, the reference electrode 706 is provided elsewhere from the wafer 702. The reference electrode 706 may include any material having a relatively stable potential. Example reference electrode materials include platinum or Ag / AgCl. Making an Ag / AgCl electrode on the surface of a substrate is well known in the art, such as (for example) the surface and electrical properties of a Ag / AgCl pseudo-reference electrode manufactured using commercially available PCB technology by Moschou et al . Characterization (Surface and Electrical Characterization of Ag / AgCl Pseudo-Reference Electrodes Manufactured with Commercially Available PCB Technologies) "(Sensors, Vol. 15 (8), 2015, pages 18102 to 18113). The analog circuit 708 may include circuits related to the operation of the sensor array 704. As such, the analog circuit 708 may be configured to provide signals to the sensor array 704 and measure signals from the sensor array 704 when interfacing with various I / O pads 716. In one embodiment, the analog circuit 708 includes a serial peripheral interface (SPI) 712 and a sensor array circuit 714. In this embodiment, an interval between the sensor array 704 and the sensor array circuit 714 is not shorter than about 135 microns. The SPI 712 may be a serial interface circuit to facilitate data transmission between the sensor array circuit 714 and an analyzer unit described in more detail below. Those skilled in the relevant arts will have a good understanding of the general operation of an SPI. The sensor array circuit 714 may include any number of reference voltage generators, operational amplifiers, low-pass filters, ADCs, and DACs to provide signals to the sensor array 704 and receive signals from the sensor array 704. In one example, the sensor array circuit 714 may be used to generate a bias reference voltage to provide a negative voltage bias of approximately -0.24 volts to a given FET sensor or FET in the sensor array 704 The body area of the sensor collection. A tunable voltage may also be provided to a given FET sensor or a liquid gate of a FET sensor set in the sensor array 704 when performing sensing. When a signal (such as Ids) received from a given FET sensor or a set of FET sensors is measured from one of the sensor arrays 704, the sensor array circuit 714 may receive the measured signal and Pass the measured signal through a transimpedance amplifier (i.e., a current / voltage converter) before outputting to an I / O pad 716 followed by one or more additional amplifier stages, low-pass filters, and finally an ADC . Noise from the measured signal can also be reduced before the measured signal is amplified by subtracting a background AC signal from the measured signal. A temperature signal (received from one or more temperature sensors in the sensor array 704) can also be amplified, filtered, and passed through an ADC before being output to an I / O pad 716. In various embodiments, a plurality of I / O pads 716 may be patterned along the periphery of the wafer 702. Much more I / O pads can be provided than the actual inputs and outputs used by the various components of the chip 702. In one embodiment, various I / O pads 716 may be coupled to another substrate or package bonded to the wafer 702 using wire bonding technology. In a particular embodiment, 32 I / O pads can be patterned around the periphery of the wafer 702. The size of a given I / O pad 716 may be approximately 80 microns by approximately 70 microns, and the spacing between the I / O pads 716 may be approximately 150 microns. An interval between the sensor array 704 and a nearest I / O pad 716 may be not shorter than about 400 microns, and an interval between the I / O pad 716 and an outermost edge of the wafer 702 may not be shorter than approximately 177.5 microns . Referring to FIG. 8, an exemplary packaging scheme for a wafer 702 is illustrated. The wafer 702 with its I / O pads 716 is bonded to a carrier layer 802. The carrier layer 802 may be another semiconductor substrate, such as a silicon substrate. In another example, the carrier layer 802 is an insulator, such as a hard plastic material. The wafer 702 may be bonded to the carrier layer 802 using any known bonding technique, such as by using solder or an adhesive. In one embodiment, the carrier layer 802 includes a plurality of through holes filled with a conductive material 804. The conductive material 804 may be any metal such as, but not limited to, tin, copper, aluminum, gold, or any alloy thereof. The conductive material 804 may include a solder bump or solder ball at one bottom surface 805 of the carrier layer 802. The solder may extend beyond the surface 805. According to an embodiment, the chip package also includes a first insulating layer 806 adjacent to one side of the chip 702. The first insulating layer 806 may also be a plastic material or resin that fills the area around the wafer 702 and assists in fixing the wafer 702 in place. In an exemplary embodiment, the first insulating layer 806 includes a via hole also filled with a conductive plug 808. The conductive plug 808 may be the same material as the conductive material 804. The conductive plug 808 is substantially aligned above the corresponding area of the conductive material 804 such that an ohmic contact is formed between the conductive plug 808 and the conductive material 804. Once the chip 702 has been fixed to the carrier layer 802 and the first insulating layer 806 surrounds it, the electrical connection 812 between the I / O pad 716 and the conductive plug 808 can be made. The electrical connection 812 may be formed using wire bonding technology, as will be understood by those skilled in the relevant art. In another example, an electrical connection 812 is formed using a lithographic patterning technique to pattern the conductive trace for electrically connecting the I / O pad 71 and a corresponding conductive plug 808. Once the electrical connection 812 is formed, a second insulating layer 810 can be deposited to protect the electrical connection 812 from environmental influences. The second insulating layer 810 may be the same material as the first insulating layer 806. The second insulating layer 810 may be a resin material flowing around the electrical connection 812 and then hardened to form a protective case. An opening 814 is formed in the second insulating layer 810 to form a path toward the sensor array existing on the wafer 702. In one embodiment where one of the reference electrodes is also patterned on the wafer 702, then the opening 814 will form a path towards the sensor array and the reference electrode. A final chip package 816 includes a wafer 702 that is bonded to the carrier layer 802 and electrically connected to various conductive solder spots or metal pads on the bottom surface 805 of the carrier layer 802. The wafer 702 is also protected from the environment through the first insulating layer 806 and the second insulating layer 810. The chip package 816 can be more easily processed and coupled to a larger substrate, such as a printed circuit board (PCB). In some embodiments, the chip package 816 may be coupled to one or more heat sinks to provide a more efficient heat dissipation path from the chip 702 to one of the surrounding air or to any of the substrates to which the chip package 816 is coupled. In other embodiments, the chip package 816 may be coupled to a Peltier device to provide thermoelectric heating and / or cooling. Referring to the illustrative embodiment of FIG. 9, a chip package 816 is bonded to a substrate 902. The substrate 902 may be a PCB including conductive contact pads for making electrical contact with solder or conductive pads on the bottom surface of the carrier layer 802. A flip-chip bonding technique may be performed to bond the chip package 816 to the surface of the substrate 902. In short, the solder or conductive pads along the bottom surface of the carrier layer 802 are aligned to the corresponding conductive pads patterned on the substrate 902 and bonded together to physically attach the chip package 816 to the substrate 902 and place The I / O pads are electrically coupled from the wafer 702 to the conductive traces present on the substrate 902. The conductive traces on the substrate 902 may be terminated in the edge connector 908. One or more edge connectors 908 may provide electrical connections to the chip 702. One or more other edge connectors 908 may provide electrical connections to a reference electrode 906 patterned on a surface of the substrate 902. Using reference electrode 906 eliminates the need to provide a reference electrode on wafer 702. Each of the one or more edge connectors 908 may be patterned using a metal such as, but not limited to, one of copper, gold, or aluminum. The reference electrode 906 can be made using techniques similar to those discussed above for the reference electrode 706 on the wafer 702. The size of the exemplary chip package 816 may be between approximately 1 to 2 cm by 1 to 2 cm or less, and the size of the substrate 902 may be between 3 to 4 cm by 3 to 4 cm or less. Illustrated above the wafer 702 is an opening 814 that exposes at least the sensor array of the wafer 702. In an exemplary embodiment, the opening 814 is substantially aligned with the reference electrode 906 along an X or Y direction, so that a liquid channel can be placed over both the opening 814 and the reference electrode 906. Liquid Design Referring to FIG. 10, a schematic diagram of an exemplary liquid cartridge 1000 is provided. This schematic diagram illustrates a top view of one of the cases 1000, and it should be noted that not all components shown are on the same horizontal plane. Moreover, the specific sizes and proportions of various liquid channels are purposely not drawn to scale for improved visualization. The box body 1000 includes a casing 1002. The housing 1002 may be formed from any plastic material, such as polymethyl methacrylate (PMMA), using injection molding, casting, or 3-D printing technology (to name a few). The housing 1002 may be formed from more than one section mechanically or through the use of an adhesive. In one embodiment, various liquid channels and chambers are formed within one or more components of the housing 1002. In another embodiment, the various liquid channels and chambers are formed from a different shaped polymer material, such as polydimethylsiloxane (PDMS). The overall size of the housing 1002 may be between about 4 cm to about 7 cm by about 4 cm to about 7 cm. As technology advances, the housing 1002 may become even smaller. In one embodiment, a substrate 902 having a packaged wafer 802 is placed within a housing 1002. In one example, only a portion of the substrate 902 is enclosed within the housing 1002, and the edge connector 908 is exposed outside the housing 1002. The liquid design of the exemplary housing 1002 includes at least a first channel 1004, a second channel 1006, and a third channel 1008. Each of the first channel 1004 and the second channel 1006 includes a corresponding liquid inlet 1010a and 1010b, respectively. The liquid inlets provide areas for injecting liquid from the outside of the case 1000 into the case 1000. The liquid inlets may also provide areas for discharging liquid from the case 1000 to the outside of the case 1000. The third channel 1008 may be aligned over the packaged wafer 802 bonded to the substrate 902. In one embodiment, the opening 814 above the sensor array is substantially within the third channel 1008. According to an embodiment, the reference electrode 906 patterned on the substrate 902 is also aligned within the third channel 1008. Each of the first channel 1004, the second channel 1006, and the third channel 1008 may have a channel width between approximately one millimeter and three millimeters. The channel height can be tied to about 1 mm. In another embodiment, one or more of the first channel 1004, the second channel 1006, and the third channel 1008 are micro liquid channels having a width and a height dimension of less than 1 mm. Each of the first channel 1004, the second channel 1006, and the third channel 1008 may have a rectangular, square, or semi-circular cross section. In some embodiments, one or more of the first channel 1004 and the second channel 1006 are connected to the third channel 1008. In this manner, liquid flowing through the first channel 1004 will eventually flow through the third channel 1008, and similarly liquid flowing through the second channel 1006 will eventually flow through the third channel 1008. In some embodiments, the third channel 1008 eventually flows into a waste chamber 1016 that collects all the liquid flowing through the box 1000. The waste chamber 1016 may include an air vent (not shown) to the atmosphere to prevent back pressure from accumulating within the liquid system. In some embodiments, each of the inlets 1010a and 1010b includes a plug 1012a and 1012b, respectively. Plug 1012a / 1012b can be a soft flexible material that fits tightly in the inlet 10l0a / 10l0b to seal the inlet and prevent any liquid leakage. The plug 1012a / 1012b may be a polymer material such as polytetrafluoroethylene (PTFE) or cork. The plugs 1012a / 1012b can seal the inlets 1010a / 1010b while allowing a capillary to pierce the plugs 1012a / 1012b without compromising the liquid seal. The capillary may be a needle-like tube, such as a syringe needle. The capillary may include a hard rigid material, such as a metal or hard plastic. The capillary-to-box 1000 coupling will be explained in more detail later when the coupling of the box 1000 to an analyzer is discussed. Cassette 1000 contains a sample inlet 1014 configured to introduce a sample into one of the first channel 1004 (as shown in FIG. 10) or the second channel 1006. In one example, a blood sample may be placed into the liquid system via the sample inlet 1014. Once the sample has been introduced, the sample inlet 1014 can be sealed using a cover or any other similar structure to provide a leak-proof seal around one of the sample inlets 1014. In the channel configuration illustrated in FIG. 10, the liquid flowing from the inlet 1010a through the first channel 1004 will be mixed with a sample introduced through the sample inlet 1014 and the mixture will be in the opening 814 and the reference electrode in the third channel 1008 Flowing above 906. Once the sample has been delivered to the sensor array exposed through the opening 814, interactions between biomolecules can occur and the FET sensor sensor can be used to detect the presence of specific analytes in the sample, or measure such Specific analyte concentration. Pressure-driven flow can be used to move liquid along and between various channels. Pressure may be caused by forcing fluid or air through one of the syringes of the cartridge 1000 or by pressurized air (to name a few) that pushes the fluid. Other examples of techniques for transporting fluid through the cartridge 1000 include electrowetting or using a peristaltic pump on a wafer. In some embodiments, liquid mixing can occur within the cartridge 1000 using any of a variety of on-wafer mixing methods known in the art. The size of the liquid channel of the box 1000 may be large enough that a certain liquid mixing occurs due to the turbulent flow of the fluid when the fluid flows through the channel. It should be understood that the location of the sample inlet 1014 may vary. For example, the sample inlet 1014 may be located directly above the opening 814 such that one of the samples introduced into the sample inlet 1014 is also introduced above the sensor array exposed through the opening 814. According to an embodiment, once the substrate 902 has been integrated into the housing 1002, the sensor array accessed via the opening 814 can be functionalized with various capture reagents. This procedure may involve flowing a fluid buffer including one of the capture reagents through the third channel 1008 so that the capture reagent has an opportunity to bind to various FET sensors in the sensor array. In another example, the capture reagent is placed directly above the opening 814 when the sample inlet 1014 is positioned above the opening 814. After the capture reagent has been immobilized, the sample inlet 1014 can be sealed so that the cartridge 1000 can be stored until it is ready to perform a biosensing test. The capture reagent may be kept in its initial buffer solution, or a fresh buffer solution may be introduced to hold the capture reagent while the cartridge 1000 is waiting for testing. Examples of different capture reagents and tests performed with capture reagents are provided herein. Referring to FIG. 11, another design of various liquid channels for the case 1000 is illustrated. In this design, a first channel 1104 having a first inlet 1102a and a second channel 1106 having an inlet 1102b meet at a region having a sample inlet 1110. One of the third channels 1108 with the opening 814 aligned therein is connected to the first channel 1104 and the second channel 1106 at the sample inlet 1110. The opening 814 provides a path down to a wafer to expose at least the sensor array on the wafer to the liquid in the third channel 1108. The liquid flowing from the first channel 1104 or the second channel 1106 through the third channel 1108 is finally collected in the waste chamber 1112. The liquid can be directed toward the waste chamber 1112 based on the geometry of the various channels or by using valves to block specific channels. The sample inlet 1110 may also be located above the opening 814. One or more of the first channel 1104, the second channel 1106, and the third channel 1108 may include a bubble trap 1114. The bubble trap 1114 may represent a region with a sudden larger profile (or a higher "ceiling") so that any air present in the solution can rise to a liquid channel in the extra space formed at the bubble trap 1114. Available and familiar to those skilled in the art will understand other bubble trap designs. It may be important to remove air bubbles from the solution before the solution reaches the sensor array below the opening 814 to ensure accurate sensing results. Referring to FIG. 12, a cartridge 1000 is illustrated coupled to one of the analyzers 1200 for performing biosensing. The cartridge 1000 can be brought into physical contact with the analyzer 1200 by, for example, pressing the cartridge 1000 against a receiving port of the analyzer 1200. The receiving port of the analyzer 1200 may include electrical pads to form ohmic contacts to some or all of the edge connectors 908. An edge of the substrate 902 can be tightly fitted into a receiving port of the analyzer 1200 so that the edge connector 908 is pressed against a corresponding conductive pad of the analyzer 1200. Other methods of assembling the box 1000 and the analyzer 1200 include snapping them together, plugging one into the other, and others. The analyzer 1200 may be small enough to be easily carried and fit into the palm of an adult hand. In some embodiments, the analyzer 1200 includes at least a first syringe 1202a and a second syringe 1202b. Each of the first syringe 1202a and the second syringe 1202b may contain a buffer or other liquid used during operation of the cartridge 1000. The syringes 1202a / 1202b each include a needle 1204a / 1204b that can be aligned to extend away from a remainder of the analyzer 1200. In some embodiments, the needles 1204a / 1204b may be aligned such that pressing the cartridge 1000 against one of the receiving ports of the analyzer 1200 causes the needles 1204a / 1204b to pierce through the corresponding plugs 1012a / 1012b and enter the inlet 1010a / 1010b. In this embodiment, the needles 1204a / 1204b are an example of piercing a capillary of the corresponding plug 1012a / 1012b. Therefore, a leak-proof seal is formed to transfer the solution from each syringe 1202a / 1202b to the corresponding inlet 1010a / 1010b of the case 1000. It should be understood that although this description only illustrates two syringes aligned with two input ports, any number of syringes and liquid input ports can be used, including an example in which only one syringe is used to couple to a single inlet. Each syringe 1202a / 1202b can be preloaded with a solution for use in various tests. In another embodiment, a user can easily remove and replace each syringe 1202a / 1202b with a different syringe. Each injector 1202a / 1202b may have its associated piston controlled via a corresponding actuator 1206a / 1206b. Examples of the actuators 1206a / 1206b include a stepping motor or an induction motor. The speed at which the actuators 1206a / 1206b press the pistons of the syringes 1202a / 1202b will directly affect the flow rate of the solution in the liquid channel of the box 1000. The actuators 1206a / 1206b can be controlled via the motor control modules 1208a / 1208b. The motor control module 1208a / 1208b includes the circuits required to generate voltages for controlling the speed and operation of the actuators 1206a / 1206b, as those skilled in the relevant art will understand. All electrical connections made to the edge connector 908 of the box 1000 can be routed to the sensing electronics 1210. The sensing electronics 1210 may include any number of discrete circuits, integrated circuits, and discrete analog circuit components designed to both provide and receive a number of different electrical signals between the sensing electronics 1210 and the edge connector 908. For example, the sensing electronics 1210 can be configured to provide power, ground, and pulse signals to the edge connector 908, which can then be used to power the sensor array and other electronics on the chip 702 And operation. The sensing electronics 1210 can also provide various voltage bias levels for activating the gates of specific FET sensors in the sensor array. The sensing electronics 1210 may receive a signal indicating a drain current measured from a specific FET sensor and a signal indicating an output from a temperature sensor on the chip 702. The sensing electronics 1210 may store this received data in a memory, or may use the received data to change the voltage bias level, or change a heat generated by a heater on the chip 702. Generally speaking, the sensing electronics 1210 controls all the signals related to the bio-sensing performed by the sensor array of the case 1000. In some embodiments, the analyzer 1200 also includes one of the functions and timing of each of the other modules controlling the analyzer 1200, such as the motor control modules 1208a / 1208b and the sensing electronics 1210. . The processor 1212 may be any type of central processing unit (CPU) or microcontroller and may be programmed by a user to perform specific functions related to the operation of the analyzer 1200. The processor 1212 may be configured to analyze a signal received from the sensing electronics 1210 to determine a concentration level of a given analyte of one of the samples from the cartridge 1000. Data related to the determined concentration level may be stored in a memory of the analyzer 1200. In another embodiment, the sensing electronics 1210 determines a concentration level of a given analyte from one of the samples in the cartridge 1000 and is further configured to store data related to the determined concentration level in One of the analyzers 1200 is in memory. In some embodiments, the analyzer 1200 includes a communication module 1214 designed to communicate data to an external processing device. The processor 1212 may be electrically coupled with the communication module 1214 to control data transmission. Communication can be wired or wireless. Examples of wired communications include data transfer via a network cable or a universal serial bus (USB) cable. Wireless communication may include radio RF transmission, Bluetooth, WiFi, 3G or 4G. The communication module 1214 may also be designed to receive data from an external processing device. For example, a program for how to operate various components of the analyzer 1200 may be transmitted to the communication module 1214 and executed by the processor 1212. The communication module 1214 may include any number of well-known hardware components to facilitate analog and / or digital data transmission and reception. After a biosensor test has been performed, the cartridge 1000 may be removed from the analyzer 1200 and discarded. In addition, the syringes 1202a / 1202b can be removed from the analyzer 1200 and discarded. Therefore, all reagents remain contained in the cartridge 1000 or the syringe 1202a / 1202b and no contamination of any other part of the analyzer 1200 occurs. In this manner, a single analyzer 1200 can be reused for testing any number of additional cassettes, where each cassette can be individually functionalized with a different capture reagent to perform a different biosensing test. In another embodiment, the syringe 1202a / 1202b is integrated on the case 1000, and the coupling between the case 1000 and the analyzer 1200 couples the associated piston of the syringe 1202a / 1202b with the actuator 1206a / on the analyzer 1200 1206b aligned. In this embodiment, the analyzer 1200 is completely free of any carried reagent containers. In another embodiment, the cartridge 1000 includes one or more capillaries that pierce the corresponding plugs 1012a / 1012b. In this embodiment, when the coupling between the cartridge 1000 and the analyzer 1200 occurs, the capillary is coupled with the remainder of the syringe 1202a / 1202b in the analyzer 1200 in a liquid manner. After a biosensing test has been performed, the cartridge 1000 with its capillaries can be removed from the analyzer 1200 and discarded. Referring to FIG. 13, an example method 1300 is presented. The method 1300 may be performed by the analyzer 1200 after the cartridge 1000 has been coupled to the analyzer 1200. Other operations related to liquid handling and electricity measurement that are not illustrated in method 1300 may be performed before, during, or after the illustrated operations of method 1300. Various operations of method 1300 may be performed in an order different from one of the illustrated sequences. In one embodiment, the method 1300 is performed after the capture reagent has been immobilized within the cartridge 1000. At block 1302, a first solution flows through a first channel of a box. The first solution can enter the box via an inlet coupled to one of the first channels. The first solution may be provided by a syringe having its needle pierced through a plug placed at the entrance of the first channel. The first solution may include a buffer solution to provide a stable pH environment. At block 1304, the dual gate backside sensing FET sensor of the sensor array is calibrated in a first solution. This calibration can be performed to measure the noise or background signal of one of the various FET sensors. This measurement can be stored and later subtracted from the measured signal when detecting biomolecules in an attempt to reduce noise and achieve a clearer detection signal. The first solution must be present above the sensor array and reference electrode patterned in the main detection channel to perform calibration. In some embodiments, the first solution does not flow during the calibration measurement. In some embodiments, the calibration measurement represents a baseline threshold voltage of the FET sensor. At block 1306, the sample is entered into the liquid network of the box via the sample inlet. The sample can be any fluid sample, including a blood sample. In some embodiments, the sample is a semi-solid sample that dissociates in solution. After the sample has been entered from the sample inlet, the sample inlet can be sealed by using a cover or other similar structure. At block 1308, a second solution flows through a second channel of the box. The second solution may be the same solution as the first solution. The second solution may traverse a path having a sample input into the liquid system at block 1306 and be mixed with the sample. The mixture of sample and second solution may then flow through the second channel and into the main detection channel in which the sensor array is located. The second solution may be a buffer solution. In one example, the second solution is a dissolution buffer solution. The pressure-driven flow can be used to move the second solution along and between channels. Pressure can be caused by forcing fluid or air through one of the syringes of the cartridge or by pressurized air (to name a few) that pushes the second solution. Other examples of techniques for delivering a second solution through the cartridge include electrowetting or using a peristaltic pump on a wafer. At block 1310, biomolecules present in the sample are cultured over the sensor array. Cultivation can last for any given amount of time, for example, between 30 seconds and 10 minutes. During the culture, the sample mixed with the second solution may not flow, or may flow at a very slow flow rate. The flow rate can be designed so that the fresh solution appears over the sensor array over time, but the flow rate is not so powerful that it cannot cause damage to the capture reagent or allow binding reactions to occur. At block 1312, after the incubation time has expired, a third solution flows through the first channel of the box and through the main detection channel to push substantially all of the sample mixed with the second solution into the waste chamber. . A third solution can be injected through the main detection channel within a given time period to ensure that the sample has been cleared from the main detection channel. The third solution used in block 1312 should ideally be the same solution as the first solution. In another embodiment, the third solution is different from the first solution. The third solution may be a buffer solution. At block 1314, the output from the sensor array is measured to determine if any binding reactions have occurred. The sensor output may be a drain current measured by one or more of the dual-gate backside sensing FET sensors in the sensor array. The measured drain current may be compared to one of the drain currents measured during calibration of the same sensor in block 1304. If the threshold voltage (e.g., approximately the voltage required to turn on the FET and cause the drain current to flow) has changed since the sensor was calibrated, it can be determined that a binding reaction has occurred and a target analyte is present in the sample in. The threshold voltage change amount and sign can depend on many factors, such as whether the dual-gate backside sensing FET sensor is an n-channel device or a p-channel device, the type of analyte detected, and the analysis The amount of positive or negative charge associated with an object. In another example, the measured output from the sensor array is the threshold voltage itself, and the threshold voltage can be compared to a threshold voltage measured during the same sensor calibration in block 1304. . Chemistry, Biology, and Interfaces The devices, systems, and methods of this disclosure as set forth in this application can be used to detect and / or monitor interactions between various entities. These interactions include biological and chemical reactions used to detect a target analyte in a test sample. As an example, reactions involving physical, chemical, biochemical, or biotransformation can be monitored to detect the production of intermediates, by-products, products, and combinations thereof. In addition, the devices, systems, and methods disclosed herein can be used in various assays (including, but not limited to, circulating tumor cell assays used in fluid biopsies) and to detect the presence of heavy metals and other environmental pollutants Chelation test). These assays and reactions can be monitored in a single format or in an array format to detect, for example, multiple target analytes. Example of Biosensing Using DGBSS FET Sensor Referring to FIG. 14, an example biosensing test is performed using the dual- gate backside sensing FET sensor described above. The probe DNA 1404 (an example of a capture reagent) is bound to the interface layer 508 via a linking molecule 1402. The linking molecule 1402 may have a reactive chemical group bonded to a portion of the interface layer 508. One example of a linker molecule includes a thiol. The linking molecules may also be formed by silylation of the surface of the interface layer 508 or by exposing the surface of the interface layer 508 to an ammonia (NH ₃ ) plasma to form reactive NH ₂ groups on the surface. The silylation process involves sequentially exposing the surface of the interface layer 508 to different chemicals to accumulate covalent binding molecules on the surface of the interface layer 508, as will be understood by those skilled in the relevant art. Probe DNA 1404 represents single-stranded DNA. According to one embodiment, the linker molecules 1402 are bonded to the interface layer 508 before any steps of the method 1300 are performed. Probe DNA 1404 can also be bound to the linker molecule 1402 before performing any of the steps of method 1300. In another example, the probe DNA 1404 is bound to the linker molecule 1402 at block 1302 of method 1300. According to an embodiment, the dual-gate backside sensing FET sensor illustrated in FIG. 14 is a FET that will be present in a sensor array on a chip, such as chip 702 described above . The bonding molecules 1402 may be bonded to the interface layer 508 before dicing a wafer-containing wafer 702 to separate the wafer 702 from the wafer. The probe DNA 1404 may be immobilized on the interface layer 508 before subjecting the FET sensor to the sample 1401. Sample 1401 may include a matched single-stranded DNA sequence 1406 that is strongly bound to its matching probe DNA 1404. The binding of the additional DNA increases the negative charge present on the interface layer 508 and directly above the channel region 208 of the FET sensor. The concept map in Figure 15A illustrates DNA binding. Here, the probe DNA with the nucleic acid sequence TCGA is bound to its complementary matching strand with the nucleic acid sequence AGCT. Any mismatched sequence will not hybridize to the probe DNA sequence. The binding of the matching DNA increases the negative charge accumulated at the interface of the interface layer 508. In the example illustrated in FIG. 15A, the interface layer 508 is hafnium oxide. FIG. 15B illustrates one of the threshold voltage shifts of the double-gate backside sensing FET sensor when the matching DNA is bound to the surface of the interface layer 508. In short, a voltage is applied to the liquid gate 510 until the FET sensor is "on" and a current flows between the drain region 206 and the source region 204. When more negative charges are present at the interface layer 508 due to complementary DNA binding, a higher voltage is required to form a conductive inversion layer in the channel region 208. Therefore, according to an embodiment, a higher voltage may be applied to the liquid gate 510 before the FET sensor is conductive and an I _ds current flows. This difference in threshold voltage can be measured and used to determine not only the presence of a target that matches the DNA sequence, but also its concentration. It should be understood that a net accumulated positive charge at one of the interface layers 508 will cause the threshold voltage to decrease rather than increase. In addition, the change in threshold voltage will have opposite sign for an n-channel FET compared to a p-channel FET. Referring to FIG. 16, another example biosensing test is performed using a dual gate backside sensing FET sensor. The probe antibody 1604 (another example of a capture reagent) is bound to the interface layer 508 via a linking molecule 1602. The linking molecule 1602 may have a reactive chemical group bonded to a portion of the interface layer 508. A sample solution 1601 may be provided above the probe antibody 1604 to determine whether a matching antigen is present in the sample solution 1601. According to an embodiment, the linking molecules 1602 are bonded to the interface layer 508 before performing any of the steps of the method 1300. The probe antibody 1604 can also be bound to the binding molecule 1602 before performing any of the steps of method 1300. In another example, a probe antibody 1604 is bound to a binding molecule 1602 at block 1302 of method 1300. Referring to FIG. 17, a binding procedure for matching antigen to probe antibody 1604 is illustrated. Here, the matched antigen will bind to the immobilized probe antibody and the unmatched antigen will not bind. Similar to the DNA hybridization procedure described above, matching the antigen will alter the accumulated charge present at the interface layer 508. The shift in threshold voltage due to the accumulated charge from the binding of the matched antibody to the probe antibody is measured in substantially the same manner as already discussed above with reference to FIG. 15B. Final remarks It should be understood that the sections of the implementation, not the summary section of this disclosure, are intended to be used to explain the scope of patent application. This disclosure abstract section may state one or more, but not all, exemplary embodiments of this disclosure as expected by the inventors, and therefore is not intended to limit the scope of this disclosure and the accompanying patent applications in any way. It should be understood that the wording or terminology herein is for the purpose of illustration and not limitation, so that the terminology or wording in this specification will be explained by those skilled in the art in view of teaching and guidance. The breadth and scope of this disclosure should not be limited by any of the exemplary embodiments set forth above, but should be defined solely in accordance with the scope of the attached application patents and their equivalents.

102‧‧‧Biosensor Box

104‧‧‧Field-Effect Transistor Sensor / Dual-Gate Backside Field-Effect Transistor / Double-Gate Backside Bio-Field-Effect Transistor / Double-Gate Backside Field-Effect Transistor Sensor

106‧‧‧ biological interface

108‧‧‧ Chip Package

110‧‧‧Liquid components

200‧‧‧Dual-gate backside sensing field effect transistor sensor

202‧‧‧Control gate / gate / gate structure

204‧‧‧Source area

206‧‧‧Drain region

208‧‧‧Aisle area / active area

210‧‧‧Isolation layer

212‧‧‧ opening

214‧‧‧ substrate

215‧‧‧Intervening dielectric

220‧‧‧ front gate

222‧‧‧back gate

300‧‧‧Addressable Array / Schematic

302‧‧‧field effect transistor / access transistor / n-channel field effect transistor

304‧‧‧Field-Effect Transistor Sensor

306‧‧‧bit line

308‧‧‧Word line

400‧‧‧ Exemplary layout

401‧‧‧Array

402‧‧‧Can be individually addressed pixels / pixels

404‧‧‧column decoder

406‧‧‧line decoder

408‧‧‧heater

410‧‧‧Temperature sensor

412‧‧‧n-channel field effect transistor / field effect transistor

500‧‧‧Dual-gate backside field effect transistor sensor

502‧‧‧metal interconnect

504‧‧‧body area

506‧‧‧Circuit / Extra Circuit

508‧‧‧Interface layer

510‧‧‧Liquid gate

512‧‧‧ solution

702‧‧‧Semiconductor wafer / wafer / wafer containing wafer

704‧‧‧Sensor array

706‧‧‧Reference electrode

708‧‧‧ analog circuit

712‧‧‧Serial peripheral interface

714‧‧‧Sensor array circuit

716‧‧‧Input / Output Pad

802‧‧‧ carrier layer / packaged chip

804‧‧‧Conductive material

805‧‧‧ bottom surface / surface

806‧‧‧first insulating layer

808‧‧‧Conductive plug

810‧‧‧Second insulation layer

812‧‧‧electrical connection

814‧‧‧ opening

816‧‧‧final chip package / chip package

902‧‧‧ substrate

906‧‧‧Reference electrode

908‧‧‧Edge Connector

1000‧‧‧Liquid Case / Box

1002‧‧‧Shell

1004‧‧‧The first channel

1006‧‧‧Second Channel

1008‧‧‧third channel

1010a‧‧‧Liquid inlet / inlet

1010b‧‧‧Liquid inlet / inlet

1012a‧‧‧plug

1012b‧‧‧plug

1014‧‧‧Sample entrance

1016‧‧‧ Waste Room

1102a‧‧‧First Entrance

1102b‧‧‧ Entrance

1104‧‧‧First channel

1106‧‧‧Second Channel

1108‧‧‧Third channel

1110‧‧‧Sample entrance

1112‧‧‧ Waste Room

1114‧‧‧ Bubble Trap

1200‧‧‧ Analyzer

1202a‧‧‧First syringe / syringe

1202b‧‧‧Second syringe / syringe

1204a‧‧‧ needle

1204b‧‧‧pin

1206a‧‧‧Actuator

1206b‧‧‧Actuator

1208a‧‧‧Motor Control Module

1208b‧‧‧Motor control module

1210‧‧‧ Sensing Electronics

1212‧‧‧Processor

1214‧‧‧Communication Module

1401‧‧‧Sample

1402‧‧‧ Linker

1404‧‧‧Probe DNA / Matching Probe DNA

1406‧‧‧ matches single-stranded DNA sequence

1601‧‧‧Sample solution

1602‧‧‧ Linker

1604‧‧‧Probe antibodies

I _ds ‧‧‧ current

The aspect of the present disclosure is best understood from the following detailed description when read with the accompanying drawings. It should be noted that according to industry standard practice, various components are not drawn to scale. In fact, for clarity of discussion, the dimensions of various components can be arbitrarily increased or decreased. FIG. 1 is a diagram illustrating components of an exemplary biosensor cartridge. FIG. 2 is a cross-sectional view of an exemplary dual-gate backside sensing FET sensor. FIG. 3 is a circuit diagram of one of a plurality of FET sensors configured as an exemplary addressable array. 4 is a circuit diagram of an exemplary addressable array of a dual-gate FET sensor and heater. 5 is a cross-sectional view of an exemplary double-gate backside sensing FET sensor configured as a pH sensor. FIG. 6A illustrates an example of binding ions to an acceptor layer. 6B illustrates a threshold voltage change in one exemplary FET sensor based on one of pH. FIG. 7 is a plan view of an exemplary biosensor wafer. 8 shows a series of cross-sectional views illustrating a manufacturing process for mounting an exemplary biosensor wafer to a processing layer. FIG. 9 is a top view of one of the processing layers having an exemplary biosensor wafer mounted to a substrate. FIG. 10 is a schematic diagram of an exemplary liquid case having an integrated biosensor wafer. FIG. 11 is a schematic diagram of one of some liquid channels among the liquid channels in an exemplary liquid case. FIG. 12 is a schematic diagram of an exemplary liquid cartridge coupled to an analyzer. FIG. 13 is a flowchart of an exemplary method of using a liquid cartridge. 14 is a cross-sectional view of an exemplary double-gate backside sensing bioFET that detects DNA. Figure 15A illustrates the binding mechanics of DNA on the surface of a receptor. 15B illustrates a change in threshold voltage of an exemplary dual-gate backside sensing bioFET based on one of the matched analyte bindings. 16 is a cross-sectional view of an exemplary double-gate backside sensing bioFET with an antibody immobilized on its sensing layer. Figure 17 illustrates the binding mechanics of antigens and antibodies on the surface of a receptor.

Claims (9)

A liquid box body includes a substrate including a plurality of contact pads configured to be electrically coupled with an analyzer, a semiconductor wafer having a sensor array, wherein the sensor array It includes a double-gate backside sensing FET sensor array and a reference electrode; a first liquid channel having a first inlet and coupled to a second liquid channel, the second liquid channel is aligned such that The sensor array and the reference electrode are placed in the second liquid channel; a sample inlet is used to place a sample in a path of the first liquid channel or the second liquid channel; and a first A plug is placed at the first inlet and includes a flexible material configured to be pierced by a capillary but not to allow liquid to leak through the first plug. The liquid cartridge of claim 1, further comprising a third liquid channel having a second inlet. The liquid cartridge of claim 2, wherein the third liquid channel is coupled to the second liquid channel. If the liquid cartridge of claim 3 further comprises a second plug, the second plug is placed At the second inlet and includes a flexible material configured to be pierced by a capillary but not to allow liquid to leak through the second plug. The liquid cartridge of claim 4, wherein the first plug and the second plug are configured to align with a first capillary and a second capillary coupled to the analyzer, and wherein when the liquid is made The plurality of contact pads are coupled to the analyzer when the box body is in contact with the analyzer entity. The liquid cartridge of claim 5, wherein when the liquid cartridge is brought into contact with the analyzer entity, the first capillary and the second capillary pierce the first plug and the second plug, respectively. The liquid cartridge of claim 1, further comprising a waste chamber coupled to one of the second liquid channels. A liquid box body includes a first liquid channel having a first inlet and coupled to a second liquid channel. The second liquid channel is aligned such that a sensor array and a reference electrode are placed on the liquid channel. Inside the second liquid channel, wherein the sensor array includes a double-gate backside sensing FET sensor array; a sample inlet for placing a sample in the first liquid channel or the second liquid channel A path; and a first plug that is placed at the first inlet and includes a flexible material configured to be pierced by a capillary but not to allow liquid to leak through the first plug, wherein The capillary is coupled to an analyzer, and when the liquid cartridge is brought into contact with the analyzer entity The capillary pierces the first plug. An analyzer configured to be coupled with a liquid cartridge, the analyzer comprising: a syringe configured such that when the liquid cartridge is physically coupled to the analyzer, a needle of the syringe and the liquid cartridge One is aligned with the corresponding input port; the actuator is configured to control the operation of the syringe; a sensing module is configured to send and receive signals from the liquid box through a plurality of conductive pads, When the liquid box is physically coupled to the analyzer, the plurality of conductive pads contact the corresponding plurality of conductive pads on the liquid box; and a processor, which is electrically coupled to the sensing module and is configured Determining a concentration level of a given analyte from a sample in the liquid cartridge based on a signal received from the liquid cartridge; wherein the liquid cartridge includes a semiconductor wafer having a sensor array The sensor array includes a dual-gate backside sensing FET sensor array.